7, 12-dimethylbenz [a] anthracene-deoxyribonucleoside adduct formation in vivo: evidence for the formation and binding of a mono-hydroxymethyl-DMBA metabolite to rat liver DNA.
The polycyclic aromatic hydrocarbon, 7,12-dimethyl benz[a] anthracene (DMBA) is a potent carcinogen to the female Sprague-Dawley rat, and when administered under conditions that have been shown to produce cancer, resulted in extensive formation of hydrocarbon-deoxyribonucleoside adducts. Sephadex LH-20 and reverse-phase h.p.l.c. and spectrofluorometric analysis of these adducts demonstrate that at least one adducts results from the binding of 7, 12-dimethylbenz [a] anthracene-1,2,3,4-tetrahydro-3,4,-dihydroxy-1,2,-oxide. In these experiments, employing i.p. administration of the hydrocarbon, a second more polar adduct was observed. Evidence is presented that this adduct results from the formation of a monohydroxymethyl-methyl-benz [a] anthracene-A-ring-diol-epoxide. While both of the monohydroxymethyl-DMBA metabolites have been shown to bind cellular DNA following their administration this is the first evidence of monohydroxymethyl-DMBA-deoxyribonucleoside adducts being formed after the administration of DMBA per se. The evidence suggests that this more polar adduct is a 7-hydroxymethyl-12-methylbenz[a]anthracene-deoxyribonucleoside adduct.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D003853:Deoxyribonucleosides / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001551:Benz(a)Anthracenes; D003853:Deoxyribonucleosides; C018970:7-hydroxymethyl-12-methylbenz(a)anthracene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA